In the JournalsPerspective

High dose peanut patch shows promise for peanut sensitivity

Patients with peanut sensitivity who wore a 250-µg epicutaneous immunotherapy-based peanut patch had a significant treatment response compared to patients wearing patches with smaller doses or placebo, according to phase 2b trial findings recently published in JAMA.

“Numerous single-center studies [on immunotherapies] have been published; although they have demonstrated induction of varying degrees of desensitization, there is concern about significant risk of severe treatment-associated adverse reactions,” Hugh A. Sampson, MD, department of pediatrics, Icahn School of Medicine at Mount Sinai, New York City, and colleagues wrote. “Moreover, only a minority of treated patients achieve any measure of longer-term tolerance.”

Researchers performed standardized food challenges using PRACTALL criteria on 221 patients with peanut sensitivity before starting therapy and following 12, 24, and 36 months of daily peanut patch application. Patients received incremental peanut protein doses of 1, 3, 10, 30, 100 and 300 mg every half hour, with additional doses of 1,000 and 2,000 mg of peanut protein for challenges at 12, 24, and 36 months. One more dose of 1,600 mg of peanut protein was administered at 24 and 36 months. Food challenges were stopped, and eliciting doses determined only when symptoms were present, according to researchers.

Sampson and colleagues randomly assigned these patients to receive an epicutaneous immunotherapy-based peanut patch containing 50 µg (n = 53), 100 µg (n = 56), or 250 µg (n = 56) of peanut protein or a placebo patch (n = 56) for 12 months. The patches were applied on children’s backs and adolescents’ and adults’ inner upper arms each day. The first patch was administered under a researcher’s supervision; all other patches were self-applied at home daily for 3, 6, and 12 hours per day during the first, second and third weeks, respectively, then for 24 hours each day.

Primary endpoints were percentage of treatment responders — those with an eliciting dose of 10-times increase or more and/or reaching 1,000 mg or more of peanut protein — in each peanut patch group vs. those using a placebo after 1 year. Secondary endpoints included treatment-emergent adverse events and percentage of responders by age group.

Researchers observed a significant absolute difference in response rates at month 12 between the 250-µg patches vs. placebo patches (difference = 25%; 95% CI, 7.7-42.3). No significant difference was seen between the placebo patch vs. the 100-µg patch. The 50-µg patch was not compared to placebo due to statistical testing hierarchical rules. The response rate difference between the 250-µg patch vs. placebo was only significant in the 6- to 11-year-old group (difference = 34.2%; 95% CI, 11.1-57.3).

In addition, no dose-related serious adverse events were observed. The percentage of patients with one or more treatment-emergent adverse events in year 1 was similar, and mostly comprised local skin reactions across all age groups. In addition, the study dropout rate for such events was 0.9% and the overall median study adherence was 97.6% after 1 year.

“To our knowledge, this is the largest trial to use the PRACTALL food challenge guidelines,” researchers wrote. “This phase 2b trial and extension study, which included an older and significantly larger patient population enrolled in more diverse study sites in North America and Europe, further validated the clinical efficacy, serological changes, safety, and compliance reported in the Consortium of Food Allergy Research epicutaneous immunotherapy trial.”

“These findings warrant a phase 3 trial,” Sampson and colleagues concluded. – by Janel Miller

Disclosures: Please see the study for a full list of the authors’ relevant financial disclosures.

Patients with peanut sensitivity who wore a 250-µg epicutaneous immunotherapy-based peanut patch had a significant treatment response compared to patients wearing patches with smaller doses or placebo, according to phase 2b trial findings recently published in JAMA.

“Numerous single-center studies [on immunotherapies] have been published; although they have demonstrated induction of varying degrees of desensitization, there is concern about significant risk of severe treatment-associated adverse reactions,” Hugh A. Sampson, MD, department of pediatrics, Icahn School of Medicine at Mount Sinai, New York City, and colleagues wrote. “Moreover, only a minority of treated patients achieve any measure of longer-term tolerance.”

Researchers performed standardized food challenges using PRACTALL criteria on 221 patients with peanut sensitivity before starting therapy and following 12, 24, and 36 months of daily peanut patch application. Patients received incremental peanut protein doses of 1, 3, 10, 30, 100 and 300 mg every half hour, with additional doses of 1,000 and 2,000 mg of peanut protein for challenges at 12, 24, and 36 months. One more dose of 1,600 mg of peanut protein was administered at 24 and 36 months. Food challenges were stopped, and eliciting doses determined only when symptoms were present, according to researchers.

Sampson and colleagues randomly assigned these patients to receive an epicutaneous immunotherapy-based peanut patch containing 50 µg (n = 53), 100 µg (n = 56), or 250 µg (n = 56) of peanut protein or a placebo patch (n = 56) for 12 months. The patches were applied on children’s backs and adolescents’ and adults’ inner upper arms each day. The first patch was administered under a researcher’s supervision; all other patches were self-applied at home daily for 3, 6, and 12 hours per day during the first, second and third weeks, respectively, then for 24 hours each day.

Primary endpoints were percentage of treatment responders — those with an eliciting dose of 10-times increase or more and/or reaching 1,000 mg or more of peanut protein — in each peanut patch group vs. those using a placebo after 1 year. Secondary endpoints included treatment-emergent adverse events and percentage of responders by age group.

Researchers observed a significant absolute difference in response rates at month 12 between the 250-µg patches vs. placebo patches (difference = 25%; 95% CI, 7.7-42.3). No significant difference was seen between the placebo patch vs. the 100-µg patch. The 50-µg patch was not compared to placebo due to statistical testing hierarchical rules. The response rate difference between the 250-µg patch vs. placebo was only significant in the 6- to 11-year-old group (difference = 34.2%; 95% CI, 11.1-57.3).

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In addition, no dose-related serious adverse events were observed. The percentage of patients with one or more treatment-emergent adverse events in year 1 was similar, and mostly comprised local skin reactions across all age groups. In addition, the study dropout rate for such events was 0.9% and the overall median study adherence was 97.6% after 1 year.

“To our knowledge, this is the largest trial to use the PRACTALL food challenge guidelines,” researchers wrote. “This phase 2b trial and extension study, which included an older and significantly larger patient population enrolled in more diverse study sites in North America and Europe, further validated the clinical efficacy, serological changes, safety, and compliance reported in the Consortium of Food Allergy Research epicutaneous immunotherapy trial.”

“These findings warrant a phase 3 trial,” Sampson and colleagues concluded. – by Janel Miller

Disclosures: Please see the study for a full list of the authors’ relevant financial disclosures.

    Perspective

    Matthew Greenhawt

    Peanut allergy is a potentially severe allergy which affects approximately 2% of U.S. children, may be lifelong for about 75%, and has no known cure. For these reasons, the FDA has fast-tracked two potential peanut allergy treatments, oral immunotherapy and the transdermal epicutaneous immunotherapy patch (both aiming to desensitize an allergic patient, protecting against small accidental exposures to peanut). Though oral immunotherapy has more robust data available from several trials, few data are available on epicutaneous immunotherapy.  This is what makes the reporting of this phase 2b randomized, placebo-controlled study of three potential doses of peanut epicutaneous immunotherapy 50 µg, 100 µg, and 250 µg) so crucial.

    All phase 2studies are works-in-progress within small but adequately powered samples, and must be interpreted cautiously.  This study demonstrated good efficacy for desensitization with the 250 µg dose of peanut epicutaneous immunotherapy in the 6-to 11year-old strata — a key target population, which is now being exclusively studied in a phase 3 trial. Unlike prior oral immunotherapy data, epicutaneous immunotherapy  appears to have a more heterogeneous effect with respect to dose and age, an important finding.  Further work is required to demonstrate what dose can effectively desensitize adolescents and adults. However, in 6- to 11-year-olds, there was a mean fivefold increase in peanut tolerance, which is exceptionally promising, and justifies further study. Moreover, though interpreting the open-label follow-up is difficult due to lack of a placebo control and large drop-out, the trend of increasing response through year 3 is promising, with longer duration of wear. Thus, the future is bright for this product as a potential therapy, as its phase 3trial in 4-to 11-year-olds is ongoing.

    • Matthew Greenhawt, MD
    • departments of allergy and immunology and pediatrics, Children’s Hospital, Colorado
      Chair, food allergy committee, American College of Allergy, Asthma and Immunology

    Disclosures: Greenhawt reports receiving grant funding from the Agency for Healthcare Quality and Research; serving as a panel and coordinating committee member of the National Institute of Allergy and Infectious Disease-sponsored Guidelines for Peanut Allergy Prevention; consulting for the Canadian Transportation Agency, Thermo Fisher, Intrommune, and Aimmune Therapeutics; serving on the physician/medical advisory boards for Aimmune Therapeutics, DBV Technologies, Nutricia, Kaleo Pharmaceutical, Nestle, and Monsanto; being a member of the scientific advisory council for the National Peanut Board; receiving honorarium for lectures from Thermo Fisher, Before Brands, and being a member of the Joint Taskforce on Allergy Practice Parameters.

    Perspective

    Ron Saff

    Many allergists, are very excited about the possibility of a new epicutaneous immunotherapy patch for patients with peanut allergy. This patch is the only potentially new therapy that we have had since peanut allergy was discovered. It has gathered a lot of attention at recent allergy conventions and there have been numerous lectures about its possibility to make a significant impact in the lives of those who are peanut-allergic. 

    Although deaths from peanut allergy are uncommon, ED visits for severe allergic reactions are common. Approximately 1% of the population is allergic to peanuts and we know that there is a genetic component, so if one parent is allergic to foods, that confers an increased risk for the child. If both parents are allergic to foods, then the chance of food allergy is even higher but peanut allergy can develop even in children that have parents with no allergy at all. It is estimated that approximately 150 to 200 people die of food allergic reactions a year with about 50% of those being caused by peanut allergies. My advice to patients now is the same advice that I gave when I first starting practicing medicine 25 years ago: it is important to watch what you eat, read food ingredient labels carefully, and of course, to carry your self-injectable epinephrine at all times. 

    As a practicing clinician who sees peanut allergic patients on a daily basis, I do have some concerns about the epicutaneous immunotherapy patch.  Will it be affordable? Will it provide my patients with a false sense of security? The epicutaneous immunotherapy patch is not designed for patients to protect them against large amounts of peanut in their diet, it is meant to protect patients who become forgetful and ingest small amounts accidentally.

    It should also be emphasized that studies involving the epicutaneous immunotherapy patch are in the relatively early stages.  Certainly, more studies are needed. Sampson and colleagues’ study had several limitations. Specifically, it excluded patients with a history of very severe food allergic reactions the group of patients we worry about the most. Additionally, this study was not designed to see what age group would receive the best protection, so we do not know if the patch will work better on young children, teenagers, or adults. I am cautiously optimistic about the epicutaneous immunotherapy patch’s chances for FDA approval because so far the results are quite promising. If the epicutaneous immunotherapy-based peanut patch is approved by the FDA,  it will most likely help a peanut allergic individual in the event of accidental ingestion.   As a medical student, I was trained that when it comes to new therapies, you do not want to be the first doctor to prescribe a new therapy because there is always a chance that the therapy will fail. On the other hand, my instructors also taught me that you do not want to be the last doctor to prescribe a new therapy because then you would be behind the times. As a cautious optimist, I would likely prescribe this patch within 4 or 5 months of FDA approval if it seems to be working for the vast majority of patients.

    • Ron Saff, MD
    • Assistant professor of medicine, Florida State University College of Medicine, Tallahassee

    Disclosures: Saff reports no relevant financial disclosures.

    Perspective

    Sarena Sawlani

    The authors of this JAMA study deserve great credit for the completing such a difficult study. The challenge of conducting a blinded, placebo-controlled trial with daily patch applications for 12 months’ time is hard to overstate. 

    Epicutaneous immunotherapy is emerging as an increasingly attractive alternative to food avoidance or oral immunotherapy. The diagnosis of food allergy comes with a great burden on the patient and their family, not to mention the emotional fear and social stigma that it may bring with it. Although oral immunotherapy has been studied and practiced, there is concern of severe reactions when performing this procedure. It is exciting to see that we are continuing to see large strides in epicutaneous immunotherapy technology and application, particularly with peanut allergy in children and young adults.

    The results from Sampson and colleague’s research suggest that the highest dose peanut patch resulted in a significant treatment response compared to placebo. Keep in mind, that there was a fair rate of local skin reactions in all groups, and the placebo group demonstrated a response rate of 25% to ‘treatment’ as well. This is a remarkably high response rate for a placebo arm, and certainly raises questions about the therapy. Nevertheless, about 50% of children with the high dose patch achieved the primary endpoint, and the longer-term follow-up arm also validated the serological changes the authors were looking for.

    These findings will continue the drive to develop epicutaneous immunotherapy solutions for patients. Further studies and phase 3 trials are warranted so that we can more closely understand the implications of peanut patches and hopefully have an efficacious new treatment option for children and young adults with peanut allergies.

    • Sarena Sawlani, MD
    • Medical Director, Chicago Allergy & Asthma

    Disclosures: Sawlani reports no relevant financial disclosures.